Oncolytic adenoviruses (Ads), which are live, replication-competent viruses that can selectively replicate in tumor cells and lead to cell lysis, have been used in tumor therapy. But due to the complexity and high mutability of human tumors, it becomes a major strategy to improve the selectivity, efficacy, and safety of oncolytic Ads. The oncolytic Ads that can express short hairpin RNA, cytokines, suicide gene, and matrix-modulating proteins have higher antitumor activity than the wild type. Tumor-specific promoters, especially hTERT and HRE promoters, increase the selectivity of oncolytic Ads for tumor cells. Moreover, oncolytic Ads surface-modified by polyethylene glycol (PEG), liposomes, biodegradable nanoparticles, and polypeptides have reduced immunogenicity and hepatotoxicity and improved antitumor activity when systemically administered, and the selectivity of oncolytic Ads can be significantly increased when linking PEG to antibodies, small peptides, cytokines, and ligands. Therefore, engineered oncolytic Ads combining the advantages of viral and non-viral vectors, as well as immunotherapy, are a promising strategy for improving the efficacy of targeted virotherapy.
Adenoviridae ; genetics ; physiology ; Animals ; Humans ; Neoplasms ; therapy ; virology ; Oncolytic Virotherapy ; trends ; Virus Replication

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Humans ; Leukemia, Promyelocytic, Acute ; pathology ; Oxides ; pharmacology ; Pyrazines ; pharmacology

Adult ; Cholesteatoma, Middle Ear ; Humans ; Male

Objective cyclin D1 gene plays a significant role in regulating cell cycle progression.Suppression of cyclin D1 protcin expression can effect on cellular proliferation,distribution of cell cycle and apoptosis.This study was to determine whether this effect also existed in chronic leukemia ceil line K562 by inhibiting the expression of cyclin D1 protein through RNA interference in vetro.Methods Plasmid vectors expressing small hairpin RNA (shRNA) targeting at cyclin D1 gene were constructed and transfected into K562 cells by chitosan,cyclin D1 protein was examined by using Western blot analysis.Inhibition of cellular proliferation was evaluated hy soft agar colony formation assay.The cell cycle and apoptosis were determined by flow cytometry.Results Expression of cyclin D1 protein was markedly down-regulated and capability of colony formation was suppressed after transfection with pshRNA-419 and pshRNA-575 at 48h.Down-regulation of cyclin D1 protein could effect on distribution of cell cycle arrested at G_0/G_1 phase and markedly induce apoptosis of K562 cells.But there had no above biological effects ob- served after transfection with blank vector and control vector of m-pshRNA-790.Conclusion Down-regulation of cyclin D1 expression can inhibit growth of K562 cells,and effect on distribution of cell cycle arrested at G_0/G_1 phase.The primary results suggest that cyclin D1 gene might serve as an effective target for the treatment of leukemia.

Attention was gradually paid by biologists to the using of RNA secondary structure in the classification of microbiology and phylogenetic relationship analysis in recent years. The development around the research was summarized here briefly. And more emphasis was given to the part introducing the application of RNA secondary structure to the analysis of phylogenetic relationship.

Objective The aim of this study was to investigate the feasibility and clinical value of detecting sentinel lymph node (SLN) with combined radioisotope and blue dye method in early stage cervical cancer. Methods Between March 2005 and April 2006, 50 patients with cervical cancer, who were staged Ⅰ b and Ⅱ a by International Federation of Gynecology and Obstetrics (FIGO), underwent SLN detection with preoperative lymphoscintigraphy. A dose of 148 MBq (4×10-4L) 99Tcm-sulfur colloid (SC) was injected into the uterine cervix at 3 and 9 o'clock position with lymphoscintigraphy taken at 15-60 min after injection. Intraoperative detection of "hot spot" lymph nodes was performed with a handheld gamma probe (γ-detection). During operation, 2-4 ml metend blue dye (BD-detection) was injected into the uterine cervix at the same positions. All patients underwent hysterectomy and pelvic lymphadenectomy. The spatial and pathological relationships of the SLN samples were compared between the two methods. SPSS 13.0 was used for statistical analysis. Results The detection rate of SLN with combined radioisotope and blue dye was 96.0% (48/50). γ-detection alone was 92.0% (46/50) and BD-detection alone was 70.0% (35/50, x2=4.92, P<0.05). In 37 patients lymphoseintigraphy showed the same SLN as γ-detection did, with a coincidence rate of 74.0% (37/50). The SLN with metastases were confirmed by histopathology in 11/48 (22.9%) patients. In the remaining 37 patients with SLN negative for metastasis, there was 1 case with non-SLN showing metastasis. In the 2 patients negative for SLN, 1 was positive for non-SLN metastasis. The SLN accuracy rate was therefore 97.9% (47/48), and the negative predictive value was 97.3% (36/37) with one patient false negative. About 72.3 % (115/159) of SLN were found in obturator region, 5.0% (8/ 159) in iuteriliac region, 12.0% (19/159) in external iliac chain, 6.9% (11/159) in common iliac region and 3.8% (6/159) in parametrium. The number of left-sided SLN detected was more than that of the right (x2=5.06, P=0.021 ). Conclusion Combined radioisotope and blue dye technique is a feasible and valuable tool to detect pelvic SLN in patients with early uterine cervical malignancy.

The focus of microbiologists has moved to the rare actinomycetes.For selective isolation of rare actinomycetes that all play the important role in bioactive compounds,the approaches which involve the methods using gellan gum and flooding solution、 rehydration-centrifugation(RC)、 extremely high frequency radiation(EHF)、 bacteriophage and sucrose-gradient centrifugation were introduced in this paper.

OBJECTIVETo study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells.

METHODSY1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM-F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR).

RESULTSY1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P < 0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P < 0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P < 0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P < 0.05). Star gene expression was further enhanced after 48-h intervention (P < 0.05). However, Ost showed no effect on Cyp11a1 (P > 0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P < 0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions.

CONCLUSIONOst could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes.

Adrenal Cortex ; drug effects ; Adrenal Cortex Neoplasms ; pathology ; Animals ; Corticosterone ; biosynthesis ; Coumarins ; pharmacology ; Gene Expression ; Mice ; RNA, Messenger ; metabolism ; Tumor Cells, Cultured

Objective To observe the effects of standardized three stage rehabilitation treatment on the neu- rological deficit scores (NDS) and ADL performance of ischemic stroke patients.Methods A total of 164 ischemic stroke patients were recruited and randomly divided into a rehabilitation group and a control group.The neurological function and ADL performance of the patients were assessed by using NDS and Modified Barthcl Index (MBI) at the admission,at the end of 1st,3rd and 6th months post stroke.Results No significant differences were found be- tween the rehabilitative and the control groups with regard to NDS and MBI at admission.The NDS demonstrated a decreasing tendency,while the MBI score an increasing tendency in both groups.In the control group,significant difference of NDS was found between admission and the end of 1st month as well as between the end of the 1 st and the 3rd months.In rehabilitation group,significant difference was revealed between all the time points with regard to NDS and MBI scores.At the end of the 1st,3rd and 6th months,the MBI scores of the rehabilitation group were signifi- cantly higher than those of the control group,indicating that the ADL performance of those treated with standardized three-stage rehabilitation protocol was improved quicker than those without the protocol.Conclusion Standardized three-stage rehabilitation treatment could improve the neurological function and ADL performance of the ischemic stroke patients.

OBJECTIVETo investigate the effect of paraquat (PQ) on reactive oxygen species (ROS) and neutrophil apoptosis and its possible signal transduction pathways.

METHODSCultured neutrophils were treated with different concentrations of PQ for 6-24 h. The apoptosis rate of neutrophils and ROS content were determined by flow cytometry. The exoressions of nuclear factor kappa B (NF-κB) and Caspase 3 were detected by Western blot. These parameters were checked again after NF-κB and Caspase 3 antagonist were applied.

RESULTSPQ could boost ROS generation and depress neutrophil apoptosis significantly. At the same time PQ could enhance the expression of NF-κB and inhibit the expression of Caspase 3. These effects could be reversed by ROS inhibitor diphenyleneiodonium (DPI) and NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC).

CONCLUSIONPQ is a potent inducer of ROS and can inhibit neutrophil apoptosis by activating NF-κB and surpressing Caspase 3 activity.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cells, Cultured ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Neutrophils ; cytology ; drug effects ; Paraquat ; toxicity ; Pyrrolidines ; pharmacology ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Thiocarbamates ; pharmacology